Pacific Health Research and Education Institute (PHREI) is currently conducting 2 Net-PD studies coordinated by the University of Rochester Clinical Coordination Center and the Statistical Coordinating Center at the University of Texas School of Public Health. A Multicenter, Double-Blind, Parallel Group, Placebo-Controlled Study of Creatine in Subjects with Treated Parkinson's Disease (PD) Long-term Study-1 (LS-1): PHREI is one of 50 centers conducting the Phase III LS-1 clinical trial. This application requests funding for the three final required years of the trial. Our goal is to complete the trial with no further drop outs or individuals who are lost to follow-up. Additionally, we aim to complete all case report forms in a timely fashion without errors. It is hoped that the results of this trial wil show that the creatine treated group has less progression compared to the placebo group as measured by the global statistical test. A Multicenter, Double-Blind, Placebo-Controlled Phase II Study of Pioglitazone in Early PD (FS-ZONE): For this trial, PHREI is one of 43 sites. No additional funding is being requested for this study. Our overall aims are: 1)to complete all visit with maximum retention of subjects for the ongoing LS-1 clinical trial, in order to determine if creatine is more effective than placebo in slowing clinical decline in treated subjects with PD; 2) to successfully recruit six subjects and complete all visits for ongoing FS-ZONE clinical trial to determine whether it is futile to proceed with studying pioglitazone as a potential agent to slow progression of PD; and 3) to participate in analyses and manuscript preparation of the main outcomes for both LS-1 (global statistical test) and FS-Zone (change in total UPDRS) and secondary analyses evaluating the effects of creatine and pioglitazone on individual PD clinical measures and on safety and tolerability.